| Size | Price | Stock | Qty |
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| Targets |
The primary target of Olinciguat is soluble guanylate cyclase (sGC). It acts as a stimulator of sGC, enhancing its NO-dependent catalytic activity. By stimulating sGC, it increases the production of the intracellular second messenger cyclic GMP (cGMP). This leads to vasodilation and anti-inflammatory effects.
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| ln Vitro |
In vitro, Olinciguat has concentration-dependent stimulation of sGC in purified rat and human enzyme assays and whole-cell assays. Its stimulatory activity is measured using sGC enzyme assays that monitor the conversion of GTP to cGMP. It enhances the synthesis of cGMP in response to NO binding.
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| ln Vivo |
In vivo, Olinciguat is an orally bioavailable sGC stimulator. It has potential anti-inflammatory and vasodilating activities. It is being investigated for the treatment of cardiovascular and renal disorders, including hypertension, heart failure, and chronic kidney disease.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Olinciguat involve sGC stimulation assays using purified rat or human sGC enzyme. The compound's stimulatory activity is measured by monitoring the conversion of GTP to cGMP in the presence of NO. EC50 values are determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for Olinciguat are conducted in cells that express sGC, such as smooth muscle cells or endothelial cells. Cells are treated with the compound, and cGMP levels are measured using immunoassays or other methods. Its effects on NO-mediated signaling and vasodilation are assessed.
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| Animal Protocol |
In vivo animal studies for Olinciguat are conducted in animal models of hypertension, heart failure, or chronic kidney disease. Animals are administered the compound orally, and blood pressure, cardiac function, and renal function are monitored. Its effects on cGMP levels in tissues are measured by biochemical assays.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Olinciguat indicate it has a molecular weight of 484.39 and a molecular formula of C21H16F5N7O3. It is orally bioavailable. Its bioavailability and other PK parameters are well-characterized from preclinical studies. The compound is typically stored as a powder at appropriate conditions.
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| Toxicity/Toxicokinetics |
Toxicological information for Olinciguat is derived from preclinical studies. As an sGC stimulator, it may cause hypotension and other cardiovascular effects. Comprehensive toxicology studies would be required for clinical development, including assessments of its effects on blood pressure, heart rate, and renal function.
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| References | |
| Additional Infomation |
Olinciguat is being investigated in the clinical trial NCT03892499 (an evaluation of the effects of the CYP3A4 inhibitor itraconazole (ITZ) on the pharmacokinetics of the soluble guanylate cyclase stimulant olinciguat (IW-1701) in healthy volunteers). Olinciguat is an orally bioavailable soluble guanylate cyclase (sGC) stimulant with potential anti-inflammatory and vasodilatory activities. After oral administration, olinciguat targets sGC and binds to it via allosteric binding, enhancing its nitric oxide (NO)-dependent catalytic activity. This enhances NO-sGC signaling and increases the production of the intracellular second messenger cyclic guanosine monophosphate (cGMP), derived from guanosine triphosphate (GTP). This enhances NO/cGMP-mediated muscle relaxation, inhibits leukocyte-endothelial cell interactions, and promotes vascular anti-inflammatory effects. The NO/sGC/cGMP signaling pathway plays a crucial role in vasodilation, blood flow, and inflammation. sGC is a heme-containing cytoplasmic signaling enzyme that catalyzes the conversion of GTP to cGMP after NO binds to heme.
Drug Indications Treatment of sickle cell disease Olinciguat is an orally bioavailable sGC stimulator with potential for treating cardiovascular and renal disorders. It is also known as IW-1701. It enhances NO-sGC signaling and increases cGMP production. It is available from research chemical suppliers for preclinical studies. It is not approved for clinical use. |
| Molecular Formula |
C21H16F5N7O3
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|---|---|
| Molecular Weight |
509.3889
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| Exact Mass |
509.123
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| CAS # |
1628732-62-6
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| PubChem CID |
90445883
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| Appearance |
White to light yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
36
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| Complexity |
768
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC([C@](C(N([H])[H])=O)(C([H])([H])N([H])C1C(=C([H])N=C(C2C([H])=C(C3C([H])=C([H])ON=3)N(C([H])([H])C3=C([H])C([H])=C([H])C([H])=C3F)N=2)N=1)F)O[H])(F)F
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| InChi Key |
YWQFJNWMWZMXRW-HXUWFJFHSA-N
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| InChi Code |
InChI=1S/C21H16F5N7O3/c22-12-4-2-1-3-11(12)9-33-16(14-5-6-36-32-14)7-15(31-33)18-28-8-13(23)17(30-18)29-10-20(35,19(27)34)21(24,25)26/h1-8,35H,9-10H2,(H2,27,34)(H,28,29,30)/t20-/m1/s1
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| Chemical Name |
(2R)-3,3,3-trifluoro-2-[[[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]amino]methyl]-2-hydroxypropanamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~245.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9631 mL | 9.8157 mL | 19.6313 mL | |
| 5 mM | 0.3926 mL | 1.9631 mL | 3.9263 mL | |
| 10 mM | 0.1963 mL | 0.9816 mL | 1.9631 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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